Ppp2r5a selectively regulates B-1 cells 4610

Description B-1 cells are innate-like B cells that play a key role in natural antibody production, a first line of defense. However, the genes that selectively regulate their development, maintenance, and function remain to be more fully explored. As part of the Knock Out Mouse Program (KOMP) we conducted flow cytometric screening of spleens from young adult male and female mice (3 each) of 641 mouse strains, each harboring a known gene knockout, and their controls. A total of 56 distinct cell populations were assessed using two multicolor flow cytometric panels. Establishing and then screening a database with the results from these efforts, we identified 7 mouse strains in which B-1 cell frequencies in the spleen were significantly and selectively altered. Among these, mice lacking Ppp2r5a stood out as significantly affecting B-1 cell population in both male and female mice. Ppp2r5a encodes a regulatory subunit of protein phosphatase 2A (PP2A), a regulator of cell growth and division. To confirm and expand these findings, we conducted flow cytometric analysis on mice lacking Ppp2r5a, confirming their selective B-1 cell deficiency in spleen and bone marrow but not peritoneal cavity. In addition, we observed significant decreased serum IgM and IgG levels in female but not male KO mice. Thus, our work identifies Ppp2r5a as a gene necessary for normal B-1 cell accumulation/ maintenance in the spleen and bone marrow and their differentiation into antibody-secreting cells. Funding Sources This work was supported by NIH grants UM1OD023221 (KKCL), R21AI17872208 (NB)